Serum antibodies against intact human collagen IX are elevated at onset of rheumatoid arthritis but are not related to development of erosions.

OBJECTIVE: To measure the presence of autoantibodies binding to intact human recombinant collagen IX and assess their usefulness as a diagnostic marker and an indicator of disease activity in rheumatoid arthritis (RA). METHODS: Recombinant human full-length collagen IX (rCIX) was produced in a baculovirus expression system and purified for use in ELISA developed to detect antibodies to native and denatured collagen IX. Fifty-three patients with recent-onset rheumatoid factor-seropositive RA were analyzed for the presence of rCIX antibodies of the IgG type at the time of initial diagnosis and after 3, 6, 12, and 24 months of followup. The RA sera were accompanied by 30 controls. Associations were determined between patients' antibody titers, development of erosions in the hands and feet, and various clinical and laboratory markers. RESULTS: Serum antibody levels among patients with RA at time of diagnosis were 1.78 times higher against native rCIX (p < 0.001) and 1.71 times higher against denatured rCIX (p < 0.001) than in the controls, and they remained high during the followup. No correlation was seen between antibody levels and clinical and laboratory findings. CONCLUSION: Our data show that patients with recent-onset RA have significantly elevated levels of autoantibodies to human rCIX. These autoantibodies were observed already at the early stages of the disease, which may reflect their diagnostic potential in RA.

Delay to institution of therapy and induction of remission using single-drug or combination-disease-modifying antirheumatic drug therapy in early rheumatoid arthritis.

OBJECTIVE: To study the impacts of 1) the delay from the onset of symptoms to the institution of disease-modifying antirheumatic drug (DMARD) therapy, 2) two treatment strategies (treatment with a combination of DMARDs or with a single drug), and 3) the presence of HLA-DRB1 alleles (shared epitope) on the prediction of disease remission after 2 years in patients with early rheumatoid arthritis (RA). METHODS: In the FIN-RACo (FINnish Rheumatoid Arthritis Combination therapy) trial, 195 patients with recent-onset RA (median duration 6 months) were randomly assigned to receive either 1) a combination of DMARDs (sulfasalazine, methotrexate, hydroxychloroquine, and prednisolone) or 2) a single DMARD with or without prednisolone. The presence of a shared epitope was tested for in 165 of the 178 patients completing the study. The additional variables of age, sex, presence of rheumatoid factor, number of fulfilled American College of Rheumatology criteria for the classification of RA, and length of delay from onset of symptoms to institution of therapy were entered into a logistic regression model to determine the significant predictors for remission at 2 years. RESULTS: The delay to therapy (cut point of 4 months) was the only significant predictor for remission in patients treated using the single-DMARD strategy, while no variable was a significant predictor for remission in those treated using the combination-DMARD strategy. The frequency of achieving remission in the combination-DMARD group after 2 years was similar in patients with short (0-4 months) and long (>4 months) delay periods (11 of 26 patients and 22 of 53 patients, respectively [approximately 42% in each group]), while the corresponding frequencies in the single-DMARD group were 8 of 23 patients (35%) and 7 of 63 patients (11%) (P = 0.021). The presence of a shared epitope was not related to the induction of remission. CONCLUSION: The delay of a few months from the onset of symptoms to institution of therapy decreases the ability of the traditional single-drug strategy to induce remission in early RA.